EP2710130A1 - Système tet-on lentiviral à double promoteur très inductible - Google Patents
Système tet-on lentiviral à double promoteur très inductibleInfo
- Publication number
- EP2710130A1 EP2710130A1 EP12727326.6A EP12727326A EP2710130A1 EP 2710130 A1 EP2710130 A1 EP 2710130A1 EP 12727326 A EP12727326 A EP 12727326A EP 2710130 A1 EP2710130 A1 EP 2710130A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- promoter
- repressor
- vector
- transcriptional
- expression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
- C12N2830/005—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination repressible enhancer/promoter combination, e.g. KRAB
Abstract
Cette invention concerne des systèmes d'expression utiles pour réguler l'expression d'un gène d'intérêt basés sur l'expression constitutive du répresseur TetR original et sur l'expression du polynucléotide sous le contrôle d'un promoteur constitutif fonctionnellement lié à une séquence d'opérateur pour séquence d'opérateur de tétracycline. Le système peut être fourni sous la forme de deux polynucléotides différents, ou sous celle d'un vecteur tout-en-un. Cette invention concerne également des vecteurs, des cellules hôtes et des particules virales selon l'invention, ainsi que leurs utilisations pour la production in vitro et in vivo de produits d'intérêt ou en thérapie.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12727326.6A EP2710130B1 (fr) | 2011-05-19 | 2012-05-21 | Système de vecteur lentiviral de type "tet-on" à deux promoteurs hautement inductible |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11166754 | 2011-05-19 | ||
| EP12727326.6A EP2710130B1 (fr) | 2011-05-19 | 2012-05-21 | Système de vecteur lentiviral de type "tet-on" à deux promoteurs hautement inductible |
| PCT/EP2012/059408 WO2012156535A1 (fr) | 2011-05-19 | 2012-05-21 | Système tet-on lentiviral à double promoteur très inductible |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP2710130A1 true EP2710130A1 (fr) | 2014-03-26 |
| EP2710130B1 EP2710130B1 (fr) | 2022-06-29 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP12727326.6A Active EP2710130B1 (fr) | 2011-05-19 | 2012-05-21 | Système de vecteur lentiviral de type "tet-on" à deux promoteurs hautement inductible |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US9822379B2 (fr) |
| EP (1) | EP2710130B1 (fr) |
| ES (1) | ES2931180T3 (fr) |
| WO (1) | WO2012156535A1 (fr) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2710130B1 (fr) * | 2011-05-19 | 2022-06-29 | Fundación Pública Andaluza Progreso Y Salud | Système de vecteur lentiviral de type "tet-on" à deux promoteurs hautement inductible |
| CN105734138B (zh) * | 2015-12-16 | 2021-05-07 | 云南农业大学 | 基于四环素调控系统检测叶绿体启动子活性的方法 |
| WO2018026723A1 (fr) | 2016-08-01 | 2018-02-08 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Cellules souches pluripotentes induites humaines pour un génie genetique à haut rendement |
| WO2018083274A1 (fr) * | 2016-11-04 | 2018-05-11 | Fundación Pública Andaluza Progreso Y Salud | Système lent-on-plus pour l'expression conditionnelle dans des cellules souches humaines |
| CA3051442A1 (fr) | 2017-02-14 | 2018-08-23 | Alejandro Soto-Gutierrez | Procedes d'ingenierie de cellules souches pluripotentes induites humaines pour produire un tissu hepatique |
| WO2019169291A1 (fr) | 2018-03-02 | 2019-09-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Utilisation de l'il-34 pour traiter l'inflammation rétinienne et la neurodégénérescence |
| CN113164625A (zh) * | 2018-09-28 | 2021-07-23 | 哈佛大学的校长及成员们 | 用于基因表达的突变体反向四环素反式激活因子 |
| CN109913424B (zh) * | 2019-03-28 | 2020-10-27 | 浙江大学 | 一种包含戊型肝炎病毒复制子的人肝癌细胞系、应用及构建方法 |
| US20220228165A1 (en) * | 2019-05-10 | 2022-07-21 | Cncure Biotech Inc. | DNA Construct for Diagnosing and Treating Cancer |
| US20240026368A1 (en) * | 2020-09-02 | 2024-01-25 | University Of Utah Research Foundation | Systems and methods for controlling bacterial transcription |
| CN114134251A (zh) * | 2020-09-04 | 2022-03-04 | 西比曼生物科技（香港）有限公司 | 一种快速检测慢病毒载体滴度的方法 |
| KR102632204B1 (ko) * | 2022-03-24 | 2024-02-02 | (주)셀레브레인 | 신규 재조합 벡터 및 이의 용도 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU592529B2 (en) | 1984-04-13 | 1990-01-18 | Litton Bionetics, Inc. | Leukoregulin, an antitumor lymphokine, and its therapeutic uses |
| DE122007000007I2 (de) | 1986-04-09 | 2010-12-30 | Genzyme Corp | Genetisch transformierte Tiere, die ein gewünschtes Protein in Milch absondern |
| US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5384253A (en) | 1990-12-28 | 1995-01-24 | Dekalb Genetics Corporation | Genetic transformation of maize cells by electroporation of cells pretreated with pectin degrading enzymes |
| WO1993004169A1 (fr) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Ciblage de genes dans des cellules animales au moyen de produits de synthese d'adn isogeniques |
| US5702932A (en) | 1992-07-20 | 1997-12-30 | University Of Florida | Microinjection methods to transform arthropods with exogenous DNA |
| US5464758A (en) | 1993-06-14 | 1995-11-07 | Gossen; Manfred | Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters |
| US5866755A (en) | 1993-06-14 | 1999-02-02 | Basf Aktiengellschaft | Animals transgenic for a tetracycline-regulated transcriptional inhibitor |
| US5789156A (en) | 1993-06-14 | 1998-08-04 | Basf Ag | Tetracycline-regulated transcriptional inhibitors |
| US5650298A (en) | 1993-06-14 | 1997-07-22 | Basf Aktiengesellschaft | Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters |
| US5814618A (en) | 1993-06-14 | 1998-09-29 | Basf Aktiengesellschaft | Methods for regulating gene expression |
| US5491084A (en) | 1993-09-10 | 1996-02-13 | The Trustees Of Columbia University In The City Of New York | Uses of green-fluorescent protein |
| US5656610A (en) | 1994-06-21 | 1997-08-12 | University Of Southern California | Producing a protein in a mammal by injection of a DNA-sequence into the tongue |
| US5736524A (en) | 1994-11-14 | 1998-04-07 | Merck & Co.,. Inc. | Polynucleotide tuberculosis vaccine |
| DK0815257T3 (da) | 1995-01-31 | 2002-04-22 | Bioimage As | Fremgangsmåde til karakterisering af biologisk aktive stoffer |
| US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
| US5780448A (en) | 1995-11-07 | 1998-07-14 | Ottawa Civic Hospital Loeb Research | DNA-based vaccination of fish |
| US5945100A (en) | 1996-07-31 | 1999-08-31 | Fbp Corporation | Tumor delivery vehicles |
| WO1998010088A1 (fr) | 1996-09-06 | 1998-03-12 | Trustees Of The University Of Pennsylvania | Procede inductible de production de virus adeno-associes recombines au moyen de la polymerase t7 |
| US5981274A (en) | 1996-09-18 | 1999-11-09 | Tyrrell; D. Lorne J. | Recombinant hepatitis virus vectors |
| US5972650A (en) | 1997-06-26 | 1999-10-26 | Brigham And Women's Hospital | Tetracycline repressor regulated mammalian cell transcription and viral replication switch |
| US5994624A (en) | 1997-10-20 | 1999-11-30 | Cotton Incorporated | In planta method for the production of transgenic plants |
| US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
| DE60043889D1 (en) | 1999-06-07 | 2010-04-08 | Tet Systems Holding Gmbh & Co | Tet repressor basierte transkriptionale regulatorische proteine |
| EP2537934A3 (fr) | 2006-05-15 | 2013-04-10 | Paratek Pharmaceuticals, Inc. | Procédés de régulation de lýexpression des gènes ou produits génétiques utilisant des composés tétracyclines substitués |
| KR100952659B1 (ko) * | 2007-08-23 | 2010-04-13 | 한양대학교 산학협력단 | 테트라사이클린-조절 시스템에 의해 유전자 과발현 및 발현감소를 동시에 유도할 수 있는 렌티바이러스 벡터 |
| EP2710130B1 (fr) | 2011-05-19 | 2022-06-29 | Fundación Pública Andaluza Progreso Y Salud | Système de vecteur lentiviral de type "tet-on" à deux promoteurs hautement inductible |
-
2012
- 2012-05-21 EP EP12727326.6A patent/EP2710130B1/fr active Active
- 2012-05-21 ES ES12727326T patent/ES2931180T3/es active Active
- 2012-05-21 WO PCT/EP2012/059408 patent/WO2012156535A1/fr active Application Filing
- 2012-05-21 US US14/118,880 patent/US9822379B2/en active Active
-
2017
- 2017-10-16 US US15/785,388 patent/US10590434B2/en active Active
Non-Patent Citations (2)
| Title |
|---|
| See also references of WO2012156535A1 * |
| YAO ET AL: "Highly Efficient Regulation of Gene Expression by Tetracycline in a Replication-Defective Herpes Simplex Viral Vector", MOLECULAR THERAPY : THE JOURNAL OF THE AMERICAN SOCIETY OF GENE THERAPY, CELL PRESS, US, vol. 13, no. 6, 1 June 2006 (2006-06-01), pages 1133 - 1141, XP005469387, ISSN: 1525-0016, DOI: 10.1016/J.YMTHE.2006.01.009 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US9822379B2 (en) | 2017-11-21 |
| WO2012156535A1 (fr) | 2012-11-22 |
| ES2931180T3 (es) | 2022-12-27 |
| US20180066284A1 (en) | 2018-03-08 |
| US20140107190A1 (en) | 2014-04-17 |
| US10590434B2 (en) | 2020-03-17 |
| EP2710130B1 (fr) | 2022-06-29 |
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